1. Field of the Invention
This invention relates generally to disposable injector devices and more specifically it concerns a check valve modification to isolate pressure upon administration of medicament through a patient's skin.
2. Description of the Prior Art
In general, a number of problems and risks have been associated with the parenteral injection for at least a century. For instance, the use of a standard hollow metal needle attached to a syringe requires thirteen steps and creates health risks not only for the patient, but the medical personnel as well.
This process can only be administered by adequately trained medical personnel. The risks of incorrect dilution or dose measurement are apparent. Any failure of sterile technique may lead to infection, ultimately presenting a greater risk to the patient. The final injection step requires training and practice to achieve the correct depth and dexterity in order to deliver the injection quickly and with minimal pain. Due to the lack of trained personnel, this is a major obstacle to successful immunization campaigns.
Advancements have, in fact occurred. Today, most syringes and needles are disposable, however, such disposable syringes are routinely re-used in developing countries and by people who suffer from drug addiction. Because of this re-use, infections such as hepatitis and AIDS are at a higher risk of transmission.
Furthermore, few drugs or vaccines are injection-ready stable liquids, rather the great majority of parenteral preparations are freeze-dried, thus requiring dilution before injection and constant refrigeration during storage.
Finally, patient compliance and compliance with the leading health organizations are at issue and numerous difficulties must be conquered. When standard syringes and needles are used, patients often do not return to field stations for follow-up doses. For instance, infants, who require a series of injections, fail to return due to the pain and anxiety a needle creates. Present parenteral injection technology, the World Health Organization (WHO) claims, is incompatible with requirements for the planned Global Programme of Vaccination and Immunization (GPV) initiatives.
An estimated six additional parenteral vaccines will be recommended for childhood vaccination by the year 2005, requiring a total of 3.6 billion immunization injections per year. The total number of parenteral injections, including injected drugs as well as vaccines, will be roughly ten times this number. Major health care providers such as UNICEF, the WHO and CDC have recently confirmed the requirement of a radical new technology that can be used by personnel with minimal training and that is safer, more convenient, and more comfortable than the syringe and needle. (Jodar L., Aguado T., and Lambert P-H, (1998) Revolutionizing Immunizations Gen. Eng. News, 18, p. 6.) Criteria include: heat stability, no cold chain of refrigerators; affordable; zero risk of cross infection; individual injection devices and vaccine doses packaged together; simple and easy to use; easy and safe disposal; no wastage; minimal discomfort, and minimum volume.
Some delivery devices address these criteria. It is known to package parenteral medications in disposable, single dose delivery devices. One approach is the packaging of single doses of vaccines in simple plastic blisters or collapsible tubes with an integral hypodermic needle attached. (U.S. Pat. Nos. 4,013,073 and 4,018,222). The Uniject.TM. plastic blister device (Becton Dickinson and Co.) is another example. Known single-use injectors require medical expertise, however, and the naked needle is a drawback.
Certain single-use injectors self-destruct, thereby eliminating the temptation to re-use. Examples are disclosed in U.S. Pat. No. 3,998,224 to Chiquiar-Arias, U.S. Pat. No. 4,233,975 to Yerman, and U.S. Pat. No. 4,391,272 to Staempfli. Another example is the Soloshot.TM. syringe (manufactured by Becton Dickinson). However, drawbacks include the price, which is more expensive than a standard syringe, and the requirement of medical personnel to effectively use such a device.
Further improvements include breakable tabs and snap rings in plastic container, such as bottles, in order to prevent tampering and ensure sealing. An early example is disclosed in U.S. Pat. No. 3,407,956 to Linkletter, which shows a removable and replaceable bottle cap. The plastic cap possesses an annular bead molded to the inside, which overrides a similar bead molded on the outside of the neck of the bottle. Natural elasticity of the materials used in manufacturing the cap permit it to expand temporarily, allowing the beads to override and then to contract again immediately once the beads have passed each other. This seats the cap firmly on the container, thereby providing an effective seal.
Needleless injectors exist now as well. These injectors use a fine stream of pressurized liquid to penetrate the skin. Pain is considerably less than that experienced during a conventional injection. Early designs used high pressure throughout the injection, to punch a hole through the tough epidermis. However, the bulk of the injection could then be infused along the initial track under much lower pressure. U.S. Pat. No. 2,704,542 to Scherer and U.S. Pat. No. 3,908,651 to Fudge disclose examples of this design. Ultimately, the engineering demands of changing the pressure during the injection and resulting complexity have limited the use of such devices.
Standard high-pressure needleless jet injectors are also inherently complex, requiring precision engineering of a number of machined steel parts. Most of the designs focus on the production of robust, reliable, heavy-duty machines capable of many injections at high rates for mass immunization campaigns. See Ismach U.S. Pat. No. 3,057,349 (1959), Landau U.S. Pat. No. 4,266,541 (1981), U.S. Pat. No. 5,746,714 (1998), D'Antonio et al PCT patent WO98/17332 (1998), Parsons PCT patent WO98/15307 (1998). Infection due to cross-contamination in such jet injectors occurs, most likely due to the high pressure in the tissue. As the tissue is distended by the injection and the pressure simultaneously falls in the injector, the injector sucks the liquid which may be contaminated with blood or interstitial fluid. The development of single-use vials which insert into the jet injector addresses this problem. Such an approach may be combined with a replaceable nozzle and a vaccine fluid path of cheap plastic, as disclosed in U.S. Pat. No. 4,266,541 to Landau.
Developed under the trademark "Intraject", a mono-dose disposable jet injector by Weston Medical, UK, this injector uses a highly compressed gas in a cannister to propel the vaccine dose. See Lloyd J. S., Aguado M. T., Pre-Filled Monodose Injection Devices: A safety standard for new vaccines, or a revolution in the delivery of immunizations?, Global Programme on Vaccines and Immunization, World Health Organization, May, 1998.
It is known that extraordinary stability can be conferred on very labile biomolecules by drying them in glasses formed from certain sugars. Trehalose is one example. See U.S. Pat. No. 4,891,319 to Roser, and Colaco C., Sen S., Thangavelu M., Pinder S., and Roser, B. J., Extraordinary stability of enzymes dried in trehalose: Simplified molecular biology. Biotechnol. 10 1007-1011 (1992). A similar technique can be applied to stabilized vaccines. See Gribbon E. M., Sen S., Roser B. J. and Kampinga J., Stabilization of Vaccines Using Trehalose (Q-T4) Technology, in F. Brown, (ed) New Approaches to Stabilization of Vaccine Potency Dev Biol Stand Basel Karger 87 193-199-(1996).
More recently, glass-forming preparations utilizing sugar derivatives includes the development of stabilization brought about by the active biomolecules remaining in solid solution in the "solid solvent" phase of the glass matrix. The biomolecules remain stable due to the high viscosity of the inert glass. In these solid solutions, molecular diffusion and molecular motion are negligible. Chemical reactions, which depend on the reactive species being free to diffuse together, are non-existent. Providing the glass itself is chemically non-reactive and dry, the product typically remains stable at temperatures up to the softening point of the glass, often expressed as the "glass-transition temperature" or Tg. Molecular diffusion and degregation commence only upon the softening and melting of the glass. Even at temperatures above the Tg, damage will only occur after a certain period of time. Because degradation reactions are chemical processes with typical kinetics, the factor determining product damage is a mathematical product of the elevated temperature and the time of exposure rather than just the high temperature. Even fragile compounds in these glasses may be briefly exposed to high temperatures with insignificant damage. While the sugar glass formulations have advantages in stability over conventional parenteral preparations, other difficulties of conventional parenteral injection remain, such as dose mismeasurement, pain, and infection risk.
Also suitable for stabilization of parenteral medications (See U.S. Pat. No. 4,698,318), the phosphate glasses are typically much stronger than sugar glasses and because of this strength, phosphate glasses are often used as structural elements in bone repair. Mixtures of metal carboxylates such as the acetate salts of sodium, potassium, calcium and zinc also form excellent glasses, PCT Publication No WO90/11756. Through the use of different mixtures of individual carboxylates and different metal cations, it is possible to tailor these phosphate and carboxylate glasses to dissolve at different, specific rates in body fluids. Composed of simple chemicals normally present in the body, phosphate and carboxylate glasses exhibit low toxicity. However, a major disadvantage exists in that a high temperature is necessary to melt them. Because of this high temperature, most drugs are precluded from being incorporated in the glass in solid solution, and ultimately, their use is restricted to preformed hollow tubes which are loaded with stable powdered drugs. See U.S. Pat. Nos. 4,793,997 and 4,866,097. A difficulty exists in filling narrow tubes with dry powders, therefore, phosphate glass tubes are of large diameter. Large diameter tubes create more physical trauma upon injection, and therefore are suitable only for veterinary applications.
Several approaches address the problem of filling narrow tubes with powdered actives. The powdered drug may be suspended in a non-aqueous liquid in which it is insoluble. These suspensions flow more readily into fine capillary tubes and carry the powdered active with them. Many organic solvents such as ethanol, acetone, dichloromethane, chloroform, and toluene may be used. However, many of these industrial solvents react destructively with biological molecules. By first enclosing the actives in stabilizing sugar glasses, as disclosed in U.S. Pat. No. 5,589,167 and in Gribbon E., Hatley R., Gard T., Blair J., Kampinga J. and Roser B. Q-T4 Stabilisation and novel drug delivery formats, Conf. Report Amer. Assoc. Pharm. Soc., 10th annual meeting, Miami Beach, Fla. (1995), this difficulty is overcome.
Truly disposable liquid jet injectors have previously been developed that operate on the new principle of using only the modest pressure of the human hand to generate a brief pulse of high pressure. This brief pressure punches a narrow hole through the skin to allow the subsequent delivery of the bulk of the dose at lower pressure (Roser, B. Disposable Injector Device U.S. Pat. No. 6,102,896. These designs for a disposable liquid jet injector, however still suffer major disadvantages. Both the reservoir assembly and the injector itself need sterile manufacture and assembly into the final device. Further, the liquid reservoir and the injector device need engineering to withstand high pressure pulses. Additionally, the completion of the power stroke is completely dependent upon the maintenance of hand pressure until the full dose of liquid has been delivered.
The power derived from steady pressure from the hand, which converts to a sharp pulse of high pressure, follows the structural breaking of "snap tabs" or the sudden overcoming of the resistance of "snap rings." The liquid dose to be injected is located in a centrally located reservoir and the high pressure barrel is located in the base of the injector itself which also has the injection orifice in the base. The existing design generates instantaneous high pressure in the bore from the breaking of the "snap tabs" and the beginning of the movement of the tubular shaft in the bore is transmitted equally and undiminished in all directions throughout the fluid. This creates a pressure of approximately 5,000 psi generated in the bore to be simultaneously applied to the first end of the plunger.
This pressure, applied over a much larger cross sectional area than that of the bore, applies a greater force resisting the downward movement of the plunger. This force is of the order of 25 times that generated in the bore since the diameter of the plunger is five times that of the bore. Enormous resistance to continued movement is generated and ultimately stops the downward motion of the plunger. This defeats the purpose of the injector by arresting the power stroke. The subject of the present invention eliminates this problem.